Public health assessment of antiepileptic drug use in children

Background In recent years, 9 new antiepileptic drugs (AEDs) have become available to treat children with epilepsy. The overall aim of this thesis is to assess the use and safety of the new and conventional AEDs in children and adolescents in the UK from a public health perspective. Methods Systematic reviews of the literature to identify prescribing trends, mortality risk and safety of AEDs were carried out. Population-based pharmacoepidemiological and safety studies using the General Practice Research Database were performed on children aged 0-18 years during 1993 and 2006. Results A total of 9,560 subjects were prescribed at least one AED during the study period. The prevalence of newer AEDs in children and adolescents has increased 4-fold. Conversely, the prescribing of conventional AEDs has decreased by 28%. More females aged 12-18 years were being prescribed lamotrigine compared to carbamazepine or sodium valproate and the increase (10-fold) was much greater than for males (5-fold). The 10-fold increase in lamotrigine prescribing was mirrored by a corresponding decrease in both sodium valproate (33%) and carbamazepine (50%). The mortality study had 151 cases of death of which 81.5% had severe underlying disorders. The cause of death was attributable to epilepsy in 18 of the 151 subjects. The AEDs were probably (2) or possibly (3) associated with death in only 5 subjects, suggesting they are not a major cause of death. The high standardised mortality ratio (SMR) 22.36 showed that children prescribed AEDs for epilepsy have an increased risk of mortality compared to the age-matched general population. Children prescribed AEDs were at a very low risk of developing a severe skin adverse event (incidence rate of 2.9 per 10,000 person- years). The AEDs were probably or possibly associated with Stevens-Johnson syndrome and erythema multiforme in only 2 subjects. Conclusions As more AEDs become available, it is important that the use and safety is continually monitored. Clinicians should use the most up-to-date evidence when choosing AED treatment to help minimise future morbidity and mortality.